Fibroblast growth factor-9 modulates the expression of myelin related proteins and multiple fibroblast growth factor receptors in developing oligodendrocytes

Abstract

The effect of fibroblast growth factor (FGF)‐9 on the expression of FGF receptors (FGFR) and the major myelin proteins was examined in cultures of developing rat brain oligodendrocytes (OLs), using immunological techniques. FGFR‐1, ‐3, and ‐4 were expressed at all developmental stages but were not present in isolated myelin fractions. By contrast, FGFR‐2 protein was predominantly localized to differentiating cells and myelin. FGF‐9 altered FGFR and myelin protein levels during OL differentiation; there was increased expression of FGFR‐1 and decreased levels of both FGFR‐2 and myelin proteins. Further, FGF‐9 stimulated mitogen‐associated protein kinase (MAPK) phosphorylation. The effect of FGF‐9 on MAPK, however, was transient and less robust in progenitor cells than in differentiated oligodendrocytes. The effects of FGF‐9 and FGF‐2 on FGFR and myelin protein levels were comparable; both up‐regulated FGFR‐1, and down‐regulated FGFR‐2, CNP, PLP and MBP. These findings suggest that FGF‐9 may be important for glial cell development. J. Neurosci. Res. 61:273–287, 2000. Published 2000 Wiley‐Liss, Inc.

FGF9-induced changes in cellular redox status and HO-1 upregulation are FGFR-dependent and proceed through both ERK and AKT to induce CREB and Nrf2 activation

“…Moreover, a transient PI3K/AKT activation was found only in primary cortical neurons after FGF9 treatment compared to long-lasting ERK activation both in vitro and in vivo, suggesting a dominant role of ERK1/2 in the transduction of FGF9-FGFR signaling. This finding is consistent with the notion that FGF9-induced ERK1/2 phosphorylation via FGFR regulates the development of oligodendrocytes [39] and the migration of cerebellar granule neurons [38]. On the other hand, the inhibition of PI3K/AKT was found not only to block FGF9-induced neuroprotection but also to reduce basal neuronal viability (Fig.…”

Mice with Conditional Inactivation of Fibroblast Growth Factor Receptor-2 Signaling in Oligodendrocytes Have Normal Myelin But Display Dramatic Hyperactivity when Combined with Cnp1 Inactivation

“…Fgfr2 is of particular interest because it is abundantly expressed in vitro by mature OLs (but not progenitors) coincidentally with major myelin proteins (Bansal et al, 1996;Cohen and Chandross, 2000;Yim et al, 2001;Fortin et al, 2005). In vivo Fgfr2 is expressed by OLs in myelinated fiber tracts of adult ro-dent brain, spinal cord, and optic nerve and is present in purified myelin, whereas expression of Fgfr2 by neurons and astrocytes is low or absent (Yazaki et al, 1994;Miyake et al, 1996;Cohen and Chandross, 2000;Messersmith et al, 2000;Fortin et al, 2005).…”

“…In vivo Fgfr2 is expressed by OLs in myelinated fiber tracts of adult ro-dent brain, spinal cord, and optic nerve and is present in purified myelin, whereas expression of Fgfr2 by neurons and astrocytes is low or absent (Yazaki et al, 1994;Miyake et al, 1996;Cohen and Chandross, 2000;Messersmith et al, 2000;Fortin et al, 2005). In contrast to Fgfr2, in mature OLs, Fgfr3 and Fgfr4 proteins are absent, and Fgfr1 is found at lower levels (Yazaki et al, 1994;Bansal et al, 1996;Miyake et al, 1996;Oh et al, 2003).…”

Effects of FGF9 on embryonic Sertoli cell proliferation and testicular cord formation in the mouse

“…Positive localisation of FGFr3 in cultured embryonic Sertoli cells strengthens further the proposal that FGF9 has an important organisational role in the supporting cell lineage. The addition of FGF9 in the absence of ECM gel, may induce an up-regulation of FGFr3 as found for FGFr1 expression levels in cultured developing rat brain oligodendrocytes (Cohen and Chandross 2000). Furthermore, exposure of human fibroblasts to epidermal growth factor (EGF) has been shown to upregulate transforming growth factor beta (TGFβ) receptor (Yamane…”